Pre-folded structures govern folding pathways of human telomeric G-quadruplexes

Understanding the mechanism by which biological macromolecules fold into their functional native conformations represents a problem of fundamental interest. DNA oligonucleotides derived from human telomeric repeat d[TAGGG(TTAGGG)3] and d[TAGGG(TTAGGG)3TT] fold into G-quadruplexes through diverse steps. Varying the pH and temperature by the use of nuclear magnetic resonance and other methods enabled detection of pre-folded structures that exist in solution before completely formed G-quadruplexes upon addition of cations. Pre-folded structures are in general hard to detect, however their knowledge is crucial to set up folding pathways into final structure since they are believed to be a starting point. Unexpectedly well-defined pre-folded structures composed of base triples for both oligonucleotides were detected at certain pH and temperature. These kinds of structures were up to now only hypothesized as intermediates in the folding process. All revealed pre-folded structures irrespective of the pH and temperature exhibited one common structural feature that could govern folding process.

Atomic structures of low-complexity protein segments reveal kinked β sheets that assemble networks

Subcellular membraneless assemblies are a reinvigorated area of study in biology, with spirited scientific discussions on the forces between the low-complexity protein domains within these assemblies. To illuminate these forces, we determined the atomic structures of five segments from protein low-complexity domains associated with membraneless assemblies. Their common structural feature is the stacking of segments into kinked β sheets that pair into protofilaments. Unlike steric zippers of amyloid fibrils, the kinked sheets interact weakly through polar atoms and aromatic side chains. By computationally threading the human proteome on our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, and keratins, which are known to form networks and localize to membraneless assemblies.

Crystal structure of bis[N-(2-hydroxyethyl)-N-methyldithiocarbamato-κ2 S,S′](pyridine)zinc(II) pyridine monosolvate and its N-ethyl analogue

The common structural feature of the title compounds, [Zn(C4H8NOS2)2(C5H5N)]·C5H5N (I) and [Zn(C5H10NOS2)2(C5H5N)]·C5H5N (II), which differ by having dithiocarbamate N-bound methyl (I) and ethyl (II) groups, is the coordination of each ZnII atom by two non-symmetrically chelating dithiocarbamate ligands and by a pyridine ligand; in each case, the non-coordinating pyridine molecule is connected to the Zn-containing molecule via a (hydroxy)O—H...N(pyridine) hydrogen bond. The resulting NS4 coordination geometry is closer to a square-pyramid than a trigonal bipyramid in the case of (I), but almost intermediate between the two extremes in (II). The molecular packing features (hydroxy)O—H...O(hydroxy) hydrogen bonds, leading to supramolecular chains with a zigzag arrangement along [10-1] (I) or a helical arrangement along [010] (II). In (I), π–π [inter-centroid distances = 3.4738 (10) and 3.4848 (10) Å] between coordinating and non-coordinating pyridine molecules lead to stacks comprising alternating rings along the a axis. In (II), weaker π–π contacts occur between centrosymmetrically related pairs of coordinating pyridine molecules [inter-centroid separation = 3.9815 (14) Å]. Further interactions, including C—H...π(chelate) interactions in (I), lead to a three-dimensional architecture in each case.

Absolute Stereochemistry of the β-Hydroxy Acid Unit in Hantupeptins and Trungapeptins

The β-hydroxy/amino acid unit is a common structural feature of many bioactive marine cyanobacterial depsipeptides. In this study, the absolute stereochemistry of the β-hydroxy acid moieties in hantupeptins and trungapeptins were determined through their synthesis and HPLC analysis of the Mosher ester derivatives. Synthesis of two3-hydroxy-2-methyloctanoic acid (Hmoa) stereoisomers, (2 S,3 R)-Hmoa and (2 S,3 S)-Hmoa, were achieved using diastereoselective asymmetric method and the retention times of all four Hmoa isomers were established indirectly by RPLC-MS analysis of their Mosher ester derivative standards. Based on the retention times of the standards, the absolute configuration of the Hmoa unit in hantupeptin C (3) and trungapeptin C (6) was assigned as (2 R,3 S)- and (2 S,3 R)-Hmoa, respectively. The use of the Mosher's reagents, coupled with HPLC analysis, provided a viable alternative to the absolute stereochemical determination of β-hydroxy acid units in depsipeptides.

The ‘Tractate’ of Conversion—BT Yeb. 46‐48 and the Evolution of Conversion Procedure

Tractate Yebamoth of the Babylonian Talmud contains a long unit devoted to the procedure of conversion (Yeb 46a‐48b). Form analysis of the unit reveals its design as a ‘tractate within a tractate.’ The unit is a collection of discussions on baraitas. It follows various literary conventions, such as placing a full description of the procedure towards the end and concluding with haggadic material and a verse of comfort. A variety of methods are applied in order to identify the unique Babylonian tendencies documented in this unit. Synoptic comparison to tannaitic parallels demonstrates the growing stringency and institutionalization of the rabbinic conversion procedure. A common structural feature of each discussion is the ending with an amoraic statement that reassure the halakhic validation of the stringent views. Stammaitic comments and the overall literary structure of the unit also seem to confirm this tendency.This unit demonstrates Babylonian efforts to further reinforce the boundaries of Jewish identity. The traditions as preserved in this unit show that Babylonian proclivities were gradually attributed to earlier Palestinian authorities. The most prominent example is the institution of the court for conversion. This is a Babylonian construct, systematically presented in places where it is missing in Palestinian rabbinic sources. In our unit it is also attributed to early Palestinain amora’im, and even to a tanna. Not only did the Babylonian sages change the model of conversion from witnessed circumcision (and later immersion) to court controlled procedure, they also projected their innovations onto earlier generations.

Modelling on-axis microdiffraction to investigate crystallographic texture within high-performance polymer fibres

Radial crystallographic texture in high-performance polymeric fibres is a common structural feature. Quite why such preferred orientation should exist and how it impacts upon the mechanical properties of the fibre is still not fully understood. This study reports the use of a modelling approach to investigate radial texture in the poly(p-phenylene benzobisoxazole) fibre type. The model allows azimuthal scattering profiles to be calculated corresponding to an on-axis microdiffraction geometry. The results show that, in order to model experimental data successfully, an offset is required between theaunit-cell axis and the fibre radial direction. The origin of this offset is tentatively attributed to solvent outflow during coagulation, which aligns the planar molecular chains. Meanwhile, textural differences between different fibre types can be explained by processing differences.